Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients.
Författare
Summary, in English
A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, Gram-negative bacteria. Furthermore, using breast cancer patient tissue microarrays, we find a strong correlation between the expression of Wnt5a in malignant epithelial cells and the frequency of CD163(+) anti-inflammatory tumor-associated macrophages. In conclusion, our data point out Wnt5a as a potential target for an efficient therapeutic modality in severe human diseases as diverse as sepsis and malignancy.
Avdelning/ar
- Institutionen för translationell medicin
- Experimentell patologi, Malmö
- Tumörmikromiljö
- Infectious Diseases Research Unit
- Klinisk mikrobiologi, Malmö
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2012
Språk
Engelska
Sidor
5448-5458
Publikation/Tidskrift/Serie
Journal of immunology
Volym
188
Issue
11
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Association of Immunologists
Ämne
- Immunology in the medical area
Status
Published
Forskningsgrupp
- Experimental Pathology, Malmö
- Infectious Diseases Research Unit
- Clinical Microbiology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1550-6606